Myalgic encephalomyelitis

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Myalgic Encephalomyelitis (ME) is a chronic, inflammatory, primarily neurological disease that is multi-systemic. Frequently triggered by a viral infection, it affects the central nervous system (CNS), immune system, cardiovascular system, endocrine system, and musculoskeletal system.[1][2] It has been classified by the World Health Organization (WHO) as a neurological disease since 1969[3][4] and has occurred in both epidemic and sporadic form since at least the 1930s, although is probably much older.

A hallmark symptom of ME, Post-exertional malaise, an intolerance to previously trivial cognitive or physical effort.[5][6][7][8][9][10][11] Other key symptoms include muscle weakness and fatiguability, sleep disturbance, and cognitive dysfunction. Autonomic nervous system dysfunction is frequent, although specific symptoms vary from patient to patient and may include postural orthostatic tachycardia, orthostatic hypotension, cold intolerance and heat intolerance. Other common symptoms include muscle pain, neuropathic pain, neck and spine stiffness, and sensory symptoms including sensitivity to light, sound, touch, paraesthesia and hyperaesthesia.

Among adults, ME is more common in women than men. New onset has been observed in children as young as eight and in adults as old as eighty. Its course is usually relapsing-remitting with new symptoms occurring either in discrete relapses (or “crashes”) or accruing over time.[12] There is a progressive form of ME but it is rarer than the relapsing-remitting type.[13]

There are no approved treatments for ME in any country except for Argentina, which has approved Ampligen for the treatment of chronic fatigue syndrome.

History[edit | edit source]

ME has occurred in both epidemic and sporadic form since at least the 1930s, although is probably much older. The first recorded outbreak of epidemic myalgic encephalomyelitis was in 1934 in Los Angeles and was thought to be an outbreak of atypical polio. After the outbreak in Akureyri, Iceland in 1946, the disease came to be called "Akureyri Disease" or Icelandic disease through much of the 1940s and 1950s. It was named myalgic encephalomyelitis after London's Royal Free Hospital outbreak in 1955. Other names included benign myalgic encephalomyelitis and epidemic neuromyasthenia.

After the Incline Village outbreak in Nevada in 1984, the disease came to be called and redefined as Chronic Fatigue Syndrome. The most recent was putative outbreak was in Arizona in 1996. 

Disease name[edit | edit source]

The name myalgic encephalomyelitis was coined by Dr. Melvin Ramsay following the 1955 Royal Free Hospital outbreak[14] and is a portmanteau of several of the key signs and symptoms of the disease: myalgic (muscle pain), encephalo (brain), myel (spinal cord), itis (inflammation).[15]

Several other names have been used or proposed throughout the history of the disease, including atypical polio, Icelandic disease, benign myalgic encephalomyelitis, epidemic neuromyasthenia, chronic fatigue syndrome, and systemic exertion intolerance disease. This has lead to much confusion as a variety of names have been used at different times to describe discrete outbreaks as well as a larger and potentially more heterogenous population of sporadic cases, defined by a wide variety of case definitions.

A survey by The MEAction Network in 2016 found that the majority of patients prefer the name myalgic encephalomyelitis to other names including chronic fatigue syndrome.[16] Most government agencies and researchers around the world use the term ME/CFS.Template:Fix/category[citation needed]

Onset[edit | edit source]

Following after an incubation period of 4 to 7 days, the prodromal phase generally involve a flu-like illness with low-grade fever. In the majority but not all cases, an infection or infectious process is evident."[17] Two to seven days later, a chronic phase commences, characterized by a measurable diffuse change in the function of the central nervous system. It is this second phase, persistent phase that most M.E."[18]

In some patients, the initial presentation involved a severe, incapacitating prolonged illness. In others, an apparent remission was followed by relapses brought on by exertion, menstrual period, or cold.

Signs and symptoms[edit | edit source]

Symptoms can range from mild to very severe and can include:

Symptoms presentation and severity can vary considerably day to day and even hour to hour.[19] Overexertion can make all symptoms worse, the effects are often delayed and may not be seen within 24 hours.[20] [21] The US National Institutes of Health notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.[22]

Post-exertional malaise[edit | edit source]

A core symptom, Post-exertional malaise, is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.[5][6][7][8][9][10][11]

Clinical findings[edit | edit source]

Although there is no definitive biomarker, several signs and findings have been frequently observed in clinical settings:

Diagnosis[edit | edit source]

There are several proposed criteria for diagnosing ME including the International Consensus Criteria (ICC) and the Canadian Consensus Criteria (CCC). The original criteria developed by Melvin Ramsay, the Ramsay definition, is not used for diagnosing ME today.

Other diagnostic criteria[edit | edit source]

Several, overly broad criteria have been proposed and are in use. These criteria likely capture some patients with the disease characterized in the medical literature on epidemic ME, exclude others, and also include patients with a wide range of other undiagnosed conditions including cancer, depression, and a range of autoimmune diseases. The United Kingdom's Oxford criteria is the broadest and likely most heterogenous definition. (The US Institute of Medicine report called for its complete retirement[23]). The US Centers for Disease Control's Fukuda criteria, in use since 1994, is also overly broad.

Differential diagnosis[edit | edit source]

The signs and symptoms of ME can be similar to other medical problems, "such as cancer, multiple sclerosis, lupus, brucellosis, or another condition."[24] Additional testing may be needed to help distinguish ME from these other problems.

Course & Prognosis[edit | edit source]

ME relapses are often a result of over-activity, but can occur without warning with no obvious inciting factors. Exposure to increased sensory information in light, sound, and movement can provoke a sensory storm.

Infections, such as the common cold, influenza and gastroenteritis, also increase the risk for a relapse. Heat and cold can transiently increase symptoms.

Pregnancy can directly affect the susceptibility for relapse. Later pregnancy appears to offer a natural protection against relapses, and there are anecdotal reports of postpartum remission. However, pregnancy does not seem to influence long-term disability.

"The later course of ME. is difficult to predict, and may either become consistently severe, improve to a plateau, or be markedly relapse-remitting. In some, even prolonged severe incapacitation can be relieved by unpredictable remission, although relapse is always possible. The degree of impairment and complexity depends on the degree of diffuse brain injury and end organ involvement."[25]

Clinical subtypes[edit | edit source]

There are no standard subtypes. Some researchers and clinicians have proposed distinguishing between a relapsing-remitting and progressive course.Template:Fix/category[citation needed] However, it is difficult to distinguish between natural variation in the population of ME patients who might share a common disease process but owing to individual, genetic, or environmental differences, have different symptom clusters or disease course versus heterogeneity created by imprecise criteria and misdiagnosis.[26]

Kerr et al proposed 7 different subsets for “CFS” as it is defined today:[27]

  • Subtype 1 This is one of the more severe subtypes. Effects are cognitive, musculoskeletal, sleep-related and anxiety/depression.
  • Subtype 2 This is one of the more severe subtypes. Effects are musculoskeletal, pain and anxiety/depression.
  • Subtype 3 This subtype has the mildest symptoms.
  • Subtype 4 This subtype is dominated by cognitive issues.
  • Subtype 5 Effects are musculoskeletal and gastrointestinal.
  • Subtype 6 This subtype is dominated by post-exertional malaise (extreme crash after exercise or exertion.)
  • Subtype 7 This is one of the more severe subtypes. Effects are pain, infections, musculoskeletal, sleep-related, neurological, gastrointestinal, neurocognitive and anxiety/depression.

Pathophysiology[edit | edit source]

ME is a multi-system disease. Numerous biological abnormalities have been found in multiple bodily system, however no common, central cause or mechanism has yet been elucidated.

Central nervous system[edit | edit source]

Radiological research on ME has shown hypoperfusion of the brain stem and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, a reduced volume of grey matter may be a result of a lack of activity and is reversible with cognitive behavior therapy.

Autonomic nervous system[edit | edit source]

Peripheral nervous system[edit | edit source]

An inquest into the death of Sophia Mirza from ME found inflammation of the dorsal spine ganglia and liver abnormalities.

Musculoskeletal system[edit | edit source]

Immune system[edit | edit source]

According to a strictly immunological explanation of CFS, the inflammatory processes triggered by T cells create leaks in the blood-brain barrier (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins such as Rnase-L. Channelopathy, a reduced ability to move metabolites in and out of cells has been implicated in this process. This may also be applicable to ME.

Chronic infection[edit | edit source]

Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the Post-polio syndrome?].

Cardiovascular[edit | edit source]

Hemodynamic abnormalities are widely found, including serum and RBC hypovolemia, NMH, and cerebral hypoperfusion. Vascular and endothelial abnormalities have been published by MERUK. However, none of these studies used research criteria for ME so the results may not be applicable to ME.

Some cardiologic features such as cardiac insufficiency, inverted T-waves and myofiber disarray have been reported in CFS and recently added to by findings of reduced Q-value. This has led clinician and researcher Dr. Paul Cheney to posit that CFS is form of partially compensated cardiomyopathy in which orthostatic intolerance and rapid fatiguability are secondary protective mechanisms. Due to the heterogeneity of the population, a single cause is unlikely, but one-third of people with ME have abnormalities when tested with Holter monitors.

Gastrointestinal system[edit | edit source]

Sex differences[edit | edit source]

A CFS/ME Norwegian study shows the disease affects all ages, with two peak ages of 10-19 years and 30-39 years; it is more common in women than in men.[28] Research by the Open Medicine Foundation cited in its paper, Metabolic features of chronic fatigue syndrome which studied severe CFS, found that the disease is different in men and women but this is not related to testosterone or estrogen. Michael VanElzakker notes there are male and female differences in neuropathic pain. A study of UK and Dutch co-horts found "younger children had a more equal gender balance compared to adolescents and adults."[29]

Risk factors and potential causes[edit | edit source]

Risk factors[edit | edit source]

Potential causes[edit | edit source]

Although risk factors for myalgic encephalomyelitis have been identified, no single definitive virus has been found in all cases, which has led to the claim that ME is a common end path of a variety of infectious insults.[30][31][32][33] It is still possible ME involves some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations.[34][35] Several theories suggest that ME is an inappropriate immune response to an infection, a theory bolstered by the observation that there is sometimes a family history of autoimmune disease.[36] There is also a shift from the Th1 type of helper T cells, which fight infection, to the Th2 type, which are more active in allergy and more likely to attack the body.[37][38]

Viruses[edit | edit source]

Other theories describe ME as an immune response to a chronic infection. The association between ME and the Coxsackie B, HHV-6, and HHV-7 viruses[39][40] [41] suggests a potential viral contribution in at least some individuals. Evidence from epidemic myalgic encephalomyelitis strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.

Bacteria[edit | edit source]

Others believe ME may sometimes result from a chronic infection with spirochetal bacteria, such as Lyme disease. Another bacterium that has been implicated in ME is Chlamydia pneumoniae.[42] Protein findings relating to several infections have seen found in the oligoclonal bands ME patients.[43]

The Vagus nerve infection hypothesis accounts for why so many different infectious onsets could be responsible. The Vagus nerve runs from the brain stem and throughout the body and has an impact on many body systems.

Given the uncertainty regarding the cause, ME and CFS patients are barred from donating blood or organs in the United Kingdom, United States and New Zealand while symptoms persist.[44][45][46][47]

Treatments[edit | edit source]

There is no known cure for ME. Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself. Success of treating symptoms of ME is not well researched or documented.

Ampligen (Approved for ME/CFS in Argentina) and Rituximab are being trialled.

ME does not have a cure, though treatments including the antiviral Ampligen (now approved for use on ME/CFS patients in Argentina) and immune system modulator Rituximab are being trialled.[48]

Epidemiology[edit | edit source]

ME has been found world-wide, in at least 75 epidemics documented in published papers from the 1930s to the 1980s.[49] Epidemics often occur in enclosed communities such as schools and hospitals.

As observed in many autoimmune disorders, ME is more common in females than males; the mean sex ratio is approxmately 2-3 females for every male.[50] In children the sex ratio is approximately equal.[51]

Co-morbidities[edit | edit source]

Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions, and increased risks for secondary diseases in patients with ME. However, as no large-scale epidemiological studies, genetic studies, or family studies have been done, there is little than can be said definitively about the rate or underlying biological reasons for potentially related conditions. Different case definitions and resulting misdiagnoses add to the confusion. Moreover, certain conditions such as postural orthostatic tachycardia syndrome (POTS) and idiopathic intracranial hypertension (IIH) are symptoms that can occur in numerous conditions, including ME. The following are some syndromes and diseases that have been associated with (or in some cases, misdiagnosed as) ME:

See also[edit | edit source]

References[edit | edit source]

  1. Myalgic Encephalomyelitis - NORD
  2. Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations Compiled by Lisa Petrison, Ph.D.Updated April 4, 2016 - PDF
  3. History of chronic fatigue syndrome - International Classifications
  4. The Terminology of ME & CFS By Professor Malcolm Hooper - PDF
  5. 5.0 5.1 ME/CFS - Pathways to Prevention - NIH
  6. 6.0 6.1 Research Descriptions of M.E. - ME Action UK
  7. 7.0 7.1 The Clinical Features of Myalgic Encephalomyelitis Melvin Ramsay, M.D., 1986
  8. 8.0 8.1 What Is Post-exertional Malaise - Very Well - Adrienne Dellwo
  9. 9.0 9.1 Post Exertional Malaise - Very Well - Adrienne Dellwo
  10. 10.0 10.1 Chronic Fatigue Syndrome - Web MD
  11. 11.0 11.1 PEM Series - Solve ME/CFS - Jenny Spotila
  12. Postexertion 'Crash,' not Fatigue per se, Marks Syndrome - MedScape
  13. Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report
  14. An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955 - The Medical Staff Of The Royal Free Hospital
  15. The Terminology of ME & CFS By Professor Malcolm Hooper
  16. MEAction RFI Poll Report (Part 1 of 3)
  17. ME Definition - Nightingale - PDF pg. 6
  18. ME Definition - Nightingale - PDF pg. 6
  19. Myalgic Encephalomyelitis - NORD
  20. What is ME - Invest in ME Research
  21. Myalgic Encephalomyelitis - NORD
  22. ME/CFS - Pathways to Prevention - Advancing the Research on Myalgic encephalomyelitis/Chronic Fatigue Syndrome
  23. US NIH Report Calls for UK Definition of ME/CFS to be Scrapped
  24. Dartmouth Hitchock - Myalgic Encephalomyelitis National Organization for Rare Disorders, Inc.
  25. What Is ME? - Disease course and clinical subtypes - A rainbow at night
  26. What Is ME? - Disease course and clinical subtypes - A rainbow at night
  27. Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes - JCP Online
  28. Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine
  29. Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed
  30. Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach - Meredyth Evans - DePaul University
  31. Vagus nerve infection hypothesis - MEpedia
  32. Chronic Fatigue Syndrome - Cleveland Clinic
  33. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. - PubMed
  34. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. RA Underhill - PubMed
  35. Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome
  36. Klimas ME/CFS Genes Study - Face Book - Video
  37. Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis - ScienceDirect
  38. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells - Biological Markers and Guided Therapy, Vol. 1, 2014, no. 1, 25 -38 - PDF
  39. Coxsackie B viruses and myalgic encephalomyelitis.
  40. Ramsay Research Team 5 – The Potential Role of HHV-6 in ME/CFS
  41. Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.
  42. Chlamydia Pneumoniae - Stanford Myalgic Encephalomyelitis/Chronic Fatigue syndrome Initiative
  43. CSF Oligoclonal Banding - NY Times
  44. People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement - ME Association
  45. American Red Cross Statement on XMRV and Chronic Fatigue Syndrome - American Red Cross
  46. Chronic fatigue patients barred from blood donation - Washington Post - By: Rob Stein - Dec 3, 2010
  47. - NZBlood
  48. Chronic Fatigue Syndrome & Myalgic Encephalomyelitis Experimental Treatments - ProHealth (Ampligen and Rituximab Tabs
  49. Myalgic Encephalomyelitis: The medical facts - What causes Myalgic Encephalomyelitis? Are there outbreaks of M.E.?
  50. Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine
  51. Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed

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From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history